Constituents of lupin seeds, like γ-conglutin and lupanine, have gained attention as potential complementary treatments for dysglycaemia management. Notwithstanding, the effect of other lupin components on carbohydrate metabolism, including β-conglutin protein, has received little attention. Here, we investigated the influence of the acute and chronic administration of β-conglutin on glycaemia modulation in normal and streptozotocin induced-to-diabetes rats. We analysed the liver transcriptome modulation exerted by β-conglutin in diabetes-induced rats using DNA microarrays to scout for potential molecular targets and pathways involved in this biological response. The acute administration of β-conglutin reduced the incremental area under the curve of glycaemia in normal and diabetes-induced animals. In a seven-day study with diabetic animals, glycaemia increased significantly in non-treated animals but remained unchanged in animals treated with a daily dose of β-conglutin. Total cholesterol was significantly lower at the end of the experimental period (−21.8 %, p = 0.039). The microarray and gene ontology analyses revealed several targets and pathways potentially modulated by β-conglutin treatment, including a possible down-regulation of Jun kinase activity. Moreover, our data indicate that targets related to oxidative stress, inflammation, and estrogenic activity might orchestrate these metabolic effects. In conclusion, our findings show that β-conglutin may help manage postprandial glycaemia and reduce cholesterol levels under the dysglycaemia stage. We identified and proposed new potential molecular targets for further research related to the mechanism of action of β-conglutin.